Drawing the Map of Life: Inside the Human Genome Project

September 9, 2010

Ten years ago the first rough draft of the human genome sequence was announced in a millennial media show that linked President Bill Clinton in the White House with Prime Minister Tony Blair in Downing Street. Their joint statement, which drew a line under an acrimonious contest between public and private gene decoding efforts, was marked by praise for a remarkable technical achievement, and the talking-up of the enormous medical benefits expected to follow from deciphering the "Book of Man", as some termed it.

Did it deserve the hype? Yes and no. Piecing together the sequence is a landmark in human self-knowledge, and the effort created a technical momentum that will soon mean we can all afford a complete sequence of our own genome - a true "genomic age", as Victor McElheny calls it in his lucid, well-balanced book. On the other hand, it also marked the last hurrah of a simple, brilliantly successful but self-limiting research programme built on a notion of DNA as a master molecule and genes' DNA sequences as the complete instruction book for making a life.

McElheny, a veteran journalist who first reported on molecular biology for the journal Science in the 1960s, is well placed to put the whole enterprise in perspective. He begins with the discovery of restriction enzymes, the first item in the toolkit that biologists would use to cut and paste DNA in the 1970s. That began a series of technical advances that allowed the notion of reading all of our own DNA to move from a gleam in the eye of a few visionaries to a real, multinational project.

It was a project full of interesting disagreements: over whether it was worth doing at all, about methods, organisation, the ownership of results and, crucially, the roles of publicly funded labs (with a big contribution in the UK from the Wellcome Trust, newly flush with cash from reorganising its endowment) and private companies. The arguments were often personal, most sharply between the main public sector players and Craig Venter, the driving force behind what became the rival private project.

Future historians will have much more to say about all of this, but McElheny gives a good basic account of it all, drawing on newspaper and journal reports, Nobel speeches and a few interviews of his own. He has had better personal access to the US public project - he is a recent biographer of its one-time director, James Watson - but appears to have not spoken to Venter. The overall picture, though, is pretty fair.

He also gives a judicious account of the results. The basic sequence was a mere prelude. The decade since has seen, as he says, "a shower of scientific surprises". These are leading to a vastly more complex picture of the evolution and operation of genomes, of a Book of Man whose annotations are constantly shifting and whose various parts interact in unexpected ways. The hitherto unexplored regions of the genome that do not code directly for functional proteins turn out to have a good deal more to do with how and when genes are expressed than anyone guessed.

The emerging details are endlessly interesting. It is too soon to say where they will lead. But the fact that they make the full sequence the beginning, not the end, of an investigation means that the promised medical applications have been slow in coming. McElheny reports the largely disappointing results of the genome-wide association studies that aimed to find new genetic links with major diseases. They did, but threw up dozens of gene locations with what are almost always weak effects. That means each one has to be pursued in much more depth to discover what it may reveal about the underlying biology of, say, heart disease, rather than offering immediate clues to prevention or treatment.

McElheny's final chapter summarises how such work may develop in several fields, but here he is aiming at a moving target and inevitably can sketch only an interim report, not a history. But the bulk of the book is an excellent summary of the beginnings of the genomic era.

Drawing the Map of Life: Inside the Human Genome Project

By Victor K. McElheny. Basic Books, 336pp, £16.99. ISBN 9780465043330. Published 1 July 2010

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